PUBLICATION

Meis cofactors control HDAC and CBP accessibility at Hox-regulated promoters during zebrafish embryogenesis

Authors
Choe, S.K., Lu, P., Nakamura, M., Lee, J., and Sagerström, C.G.
ID
ZDB-PUB-091101-11
Date
2009
Source
Developmental Cell   17(4): 561-567 (Journal)
Registered Authors
Choe, Seong-Kyu, Nakamura, Mako, Sagerström, Charles
Keywords
DEVBIO
MeSH Terms
  • Acetylation
  • Animals
  • Blotting, Western
  • CREB-Binding Protein/genetics
  • CREB-Binding Protein/metabolism*
  • Chromatin Immunoprecipitation
  • DNA-Binding Proteins/genetics
  • DNA-Binding Proteins/metabolism
  • Embryo, Nonmammalian/physiology*
  • Embryonic Development
  • Gene Expression Regulation, Developmental*
  • Histone Deacetylase 1
  • Histone Deacetylases/genetics*
  • Histone Deacetylases/metabolism
  • Histones/metabolism
  • Homeodomain Proteins/genetics*
  • Homeodomain Proteins/metabolism
  • Immunoprecipitation
  • Luciferases/metabolism
  • Promoter Regions, Genetic/genetics*
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Regulatory Sequences, Nucleic Acid
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/growth & development
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
PubMed
19853569 Full text @ Dev. Cell
Abstract
Hox proteins form complexes with Pbx and Meis cofactors to control gene expression, but the role of Meis is unclear. We demonstrate that Hoxb1-regulated promoters are highly acetylated on histone H4 (AcH4) and occupied by Hoxb1, Pbx, and Meis in zebrafish tissues where these promoters are active. Inhibition of Meis blocks gene expression and reduces AcH4 levels at these promoters, suggesting a role for Meis in maintaining AcH4. Within Hox transcription complexes, Meis binds directly to Pbx and we find that this binding displaces histone deacetylases (HDACs) from Hoxb1-regulated promoters in zebrafish embryos. Accordingly, Pbx mutants that cannot bind Meis act as repressors by recruiting HDACs and reducing AcH4 levels, while Pbx mutants that bind neither HDAC nor Meis are constitutively active and recruit CBP to increase AcH4 levels. We conclude that Meis acts, at least in part, by controlling access of HDAC and CBP to Hox-regulated promoters.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes